Ondansetron Tablets
DEFINITION
Ondansetron Tablets contain Ondansetron Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of ondansetron (C18H19N3O).
IDENTIFICATION
• A. Infrared Absorption 197K
Sample:
Transfer a portion of the powder from finely powdered Tablets, equivalent to 100 mg of ondansetron hydrochloride, to a suitable conical flask. Add 50 mL of alcohol, and swirl. Pass the liquid through a PTFE filter of 0.45-µm pore size into a 50-mL beaker. Evaporate the solvent on a rotary evaporator. Dry the precipitate in an air oven for 1 h at 105. Prepare a suitable dispersion of the residue in potassium bromide, and record the spectra of the Sample and the standard specimen in the spectral range 3800650 cm1. [NoteIt is recommended that a solution of USP Ondansetron Hydrochloride RS in alcohol be prepared at a concentration of 2 mg/mL before the evaporation, followed by the drying steps. ]
Acceptance criteria:
The Sample shows strong bands at 1621, 1481, 1281, and 758 cm1, similar to the potassium bromide dispersion of USP Ondansetron Hydrochloride RS.
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
2.7 g/L of monobasic potassium phosphate. Adjust with 1 N sodium hydroxide to a pH of 5.4.
Mobile phase:
Acetonitrile and Buffer (1:4)
Diluent:
Acetonitrile and Buffer (1:1)
Standard solution:
0.05 mg/mL of ondansetron (free base) in Diluent from USP Ondansetron Hydrochloride RS
Sample stock solution:
Weigh and finely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 50 mg of ondansetron, based on the label claim, to a 100-mL volumetric flask. Add 70 mL of Diluent, and sonicate for about 20 min. Dilute with Diluent to volume. Centrifuge a portion of the solution.
Sample solution:
Quantitatively dilute the supernatant with Diluent to obtain a solution having a nominal concentration of 0.05 mg/mL of ondansetron, based on the label claim. Pass through a suitable nylon filter of 0.45-µm pore size, and use the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 216 nm
Column:
4.6-mm × 25-cm; 5-µm packing L10
Flow rate:
1.5 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the label claim of ondansetron (C18H19N3O) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
PERFORMANCE TESTS
Change to read:
• Dissolution 711
Test 1
Medium:
Water; 500 mL, deaerated
Apparatus 2:
50 rpm
Time:
15 min
Standard solution:
USP Ondansetron Hydrochloride RS in Medium in a concentration similar to the one expected in the Sample solution
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and dilute, if necessary, with Medium.
Instrumental conditions
Mode:
UV
Analytical wavelength:
310 nm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
Tolerances:
NLT 80% (Q) of the labeled amount of C18H19N3O is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium, Apparatus 2, Standard solution, Sample solution, Instrumental conditions, and Analysis:
Proceed as directed for Test 1.
Time:
30 min
Tolerances:
NLT 80% (Q) of the labeled amount of C18H19N3O is dissolved.
Test 3:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:
0.01 N hydrochloric acid; 500 mL, deaerated
Apparatus 2:
50 rpm
Time:
30 min
Standard solution:
Known concentration of USP Ondansetron Hydrochloride RS in Medium, close to the expected concentration of the Sample solution
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and dilute, if necessary, with Medium.
Instrumental conditions
Mode:
UV
Analytical wavelength:
248 nm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
Tolerances:
NLT 80% (Q) of the labeled amount of C18H19N3O is dissolved.
Test 4:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium:
0.1 N hydrochloric acid; 500 mL
Apparatus 2:
50 rpm
Time:
30 min
Standard stock solution:
450 µg/mL of USP Ondansetron Hydrochloride RS in Medium
Standard solution:
Dilute the Standard stock solution quantitatively and stepwise, if necessary, with Medium to obtain a final concentration of about (L/500) mg/mL, where L is the Tablet label claim, in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Instrumental conditions
Mode:
UV
Analytical wavelength:
249 nm
Cell path:
1 cm for Tablets labeled to contain 4 or 8 mg; 0.2 cm for Tablets labeled to contain 16 or 24 mg
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
Tolerances:
NLT 80% (Q) of the labeled amount of ondansetron is dissolved.
Test 5:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Medium, Apparatus 2, Standard solution, Sample solution, Instrumental conditions, and Analysis:
Proceed as directed for Test 1.
Time:
30 min
Tolerances:
NLT 70% (Q) of the labeled amount of ondansetron is dissolved.
Test 6:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.
Medium:
Water; 500 mL, deaerated
Apparatus 2:
50 rpm
Time:
30 min
Buffer:
3.12 g/L of monobasic sodium phosphate dihydrate. Adjust with 1 N sodium hydroxide to a pH of 5.4.
Mobile phase:
Acetonitrile and Buffer (40:60)
Standard solution
For Tablets labeled to contain 4 or 24 mg:
0.01 mg/mL of USP Ondansetron Hydrochloride RS in Medium
For Tablets labeled to contain 8 mg:
0.02 mg/mL of USP Ondansetron Hydrochloride RS in Medium
Sample solution
For Tablets labeled to contain 4 or 8 mg:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
For Tablets labeled to contain 24 mg:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Further dilute 4.0 mL of this solution with Medium to 25.0 mL.
Chromatographic system
Mode:
LC
Detector:
UV 216 nm
Column:
4.6-mm × 5-cm; 5-µm packing L10
Flow rate:
2.0 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (rU/rS) × (CS/L) × (Mr1/Mr2) × V × D × 100
Tolerances:
NLT 75% (Q) of the labeled amount of ondansetron is dissolved.(RB 1-Jul-2011)
• Uniformity of Dosage Units 905:
Meet the requirements
IMPURITIES
• Organic Impurities
Buffer and Mobile phase:
Proceed as directed in the Assay.
System suitability solution:
0.05 and 0.1 mg/mL of USP Ondansetron Related Compound A RS and USP Ondansetron Hydrochloride RS, respectively, in Mobile phase
Standard stock solution:
Use the Standard solution in the Assay.
Standard solution:
1.5 µg/mL of ondansetron in Mobile phase from the Standard stock solution
Sample solution:
Weigh and crush NLT 20 Tablets. Transfer a quantity of powder, equivalent to 50 mg of ondansetron, to a 100-mL volumetric flask. Add about 70 mL of Mobile phase, and sonicate for about 20 min. Dilute with Mobile phase to volume. Centrifuge the solution. Pass a portion of the solution through a suitable nylon filter of 0.45-µm pore size, and use the filtrate.
Chromatographic system:
Proceed as directed in the Assay.
Run time:
At least 45 min for the Sample solution
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between ondansetron related compound A and ondansetron, System suitability solution
Relative standard deviation:
NMT 5.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria:
See Table 1.
Table 1
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers. Store at controlled room temperature.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
• USP Reference Standards 11
USP Ondansetron Related Compound A RS
3[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4122
Pharmacopeial Forum: Volume No. 34(4) Page 971
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